title: Differential dose-dependent effects of prednisolone on shedding of endothelial adhesion molecules during human endotoxemia.
abstract: Low dose prednisolone was shown to be beneficial in the treatment of the Acute respiratory distress syndrome (ARDS) and septic shock. One corticosteroid-induced effect, postulated to mediate corticosteroid-induced anti-inflammatory effects, is decreased expression of adhesion molecules on endothelial cells, thereby preventing leukocyte recruitment at inflammatory sites. The current study aimed to investigate the effect of increasing doses of prednisolone on the release of soluble adhesion molecules in healthy volunteers challenged with endotoxin. Therefore, 32 healthy, male volunteers received prednisolone orally at doses of 0mg, 3mg, 10mg or 30 mg at 2h before injection of endotoxin prepared from Escherichia coli (4 ng/kg) and levels of soluble E-selectin (sE-selectin), soluble VCAM-1 (sVCAM-1) and soluble ICAM-1 (sICAM-1) were measured. Levels of all markers were increased after induction of endotoxemia. Levels of sE-selectin were inhibited by a dose of 3mg prednisolone and levels of sVCAM-1 were decreased after a dose of 10mg. Maximal inhibition of both sE-selectin and sVCAM-1 levels was achieved by the highest dose of prednisolone 30 mg. Remarkably, prednisolone 3mg potentiated endotoxin-induced sVCAM-1 release. Levels of sICAM-1 were not affected by prednisolone. Together, the data suggest that prednisolone differentially and dose-dependently influences the release of soluble endothelial adhesion molecules during human endotoxemia.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Room G2-132, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Lucienne C
authors.initials: LC
authors.lastname: Lemaire
authors.forename: Martijn D
authors.initials: MD
authors.lastname: de Kruif
authors.forename: Ida A
authors.initials: IA
authors.lastname: Giebelen
authors.forename: Marieke A D
authors.initials: MA
authors.lastname: van Zoelen
authors.forename: Cornelis
authors.initials: C
authors.lastname: van't Veer
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000097:blood / Q000276:immunology; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008070:Lipopolysaccharides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011239:Prednisolone